Medical instrument and production thereof

ABSTRACT

A medical instrument having a blood contact portion formed of a hydrophobic material, wherein a surface-active agent safe to a human body is deposited onto part or the entirety of the blood contact portion so that the medical instrument is fully primed by introducing liquid into the instrument without leaving fine bubbles adhered to the surface of the blood contact portion. Further, a method for fabricating a medical instrument is provided, comprising steps of assembling a medical instrument having a blood contact portion formed of a hydrophobic material, and contacting a liquid containing a surface-active agent safe to a human body to the blood contact portion, followed by drying, leaving the surface-active agent deposited onto the surface of the blood contact portion so that the surface-active agent is steadily and readily deposited onto the blood contact portion of hydrophobic material.

TECHNICAL FIELD

This invention relates to a medical instrument for use in a so-calledextracorporeal circuit, wherein blood is taken out of a human body,passed through the instrument, and fed back to the human body, and to amethod for fabricating the same. Particularly, it relates to a medicalinstrument having a blood contact portion formed of a hydrophobicmaterial and a method for fabricating the same.

BACKGROUND ART

One extracorporeal circuit which has heretofore been used is anoxygenator circuit system which substitutes for the functions of theheart and lung during, for example, cardiotomy surgery. Referring toFIG. 5, the oxygenator circuit system 100 generally includes anoxygenator 1, a heat exchanger 50, a blood reservoir 31, a blood filter70, a blood line 90 interconnecting the foregoing units and a human body94, and a pump 95.

Most of the oxygenators used are membrane oxygenators. The membraneoxygenator has a gas-exchange membrane disposed in a housing such thatgas exchange is carried out by passing blood over one surface of thegas-exchange membrane and an oxygen-containing gas over the othersurface of the membrane. Most of the commonly used gas-exchangemembranes are hydrophobic membranes including hydrophobic porousmembranes formed of polypropylene, polyethylene or the like anddiffusion membranes formed of silicone rubber, etc.

In use, a priming operation is carried out to clean the interior of themembrane oxygenator and remove air therefrom before blood is passedthrough the oxygenator. It is difficult to completely remove air duringthe priming operation. Particularly with a hollow fiber oxygenator usinghydrophobic porous hollow fibers as the gas-exchange membrane, thereoccurs an air blocking phenomenon whereby air is taken into the fluidside from the gas side so that unescapable gas will stagnate betweenhollow fiber membranes on the fluid side. As a result, those portions ofhollow fiber membranes in contact with the stagnating gas do not contactblood, negating the effective use of hollow fiber membranes. Thus theoxygenator sometimes fails to exert its full gas-exchange ability. Theblood filter functions to remove foreign matter and bubbles from thegas-exchaged blood on the way back to the human body. The blood filteralso uses a hydrophobic membrane. It is thus difficult for the primingoperation to completely remove air for the same reason as with theaforementioned membrane oxygenator. Particularly, the blood filter has aproblem whereby air is left on the surface of a hydrophobic membrane toreduce the effective surface area of the hydrophobic membrane,eventually increasing the pressure loss across the blood filter.

Besides the membrane oxygenator, heat exchanger, and blood filter, bloodtubes used for fluid communication of these units to the human body aregenerally formed of flexible synthetic resins such as vinyl chloride andsilicone rubber. The aforementioned priming operation is carried outthroughout the tubes as well as the oxygenator and blood filter. Sincethe blood tubes are formed of the above-mentioned material, their insidesurface is hydrophobic. It is thus difficult to remove fine bubblesadhered to the inside surface of the tubes by the priming operation.Upon blood circulation, such bubbles will gradually enter the blood,causing blood foaming.

Further, the membrane oxygenator and blood filter include many portionsformed of hydrophobic resin in addition to their membranes. The sameapplies to other units involved in the oxygenator circuit, for example,a blood reservoir and a heat exchanger. For example, housings of themembrane oxygenator, blood filter, blood reservoir, and heat exchangerare generally formed of hydrophobic resins such as polycarbonate,polystyrene, MBS, and polypropylene. The housings thus have many bloodcontact portions of hydrophobic material. It is difficult to remove finebubbles adhered to the inside surface of the blood contact portions bythe priming operation as in the case of the inside surface of the bloodtubes mentioned above. This causes the introduction of bubbles intoblood upon blood circulation.

An object of the present invention is to provide a medical instrument inwhich air removal can be readily completed by a priming operation priorto blood circulation, leaving few bubbles adhered, as well as to providea method for fabricating the same.

DISCLOSURE OF THE INVENTION

According to the present invention, there is provided a medicalinstrument having a blood contact portion formed of a hydrophobicmaterial, characterized in that a surface-active agent safe to a humanbody is deposited onto part or the entirety of the blood contactportion.

According to the present invention, there is also provided a method forfabricating a medical instrument, comprising steps of assembling amedical instrument having a blood contact portion formed of ahydrophobic material, and contacting a liquid containing asurface-active agent safe to a human body to the blood contact portion,followed by drying, leaving the surface-active agent deposited onto thesurface of the blood contact portion.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of an embodiment in which the medicalinstrument of the present invention is applied to a membrane oxygenator.

FIG. 2 is a partial cross-sectional view of an embodiment in which themedical instrument of the present invention is applied to a membraneoxygenator system having a heat exchanger and a blood reservoircombined.

FIG. 3 is a partial cross-sectional view of an embodiment in which themedical instrument of the present invention is applied to a bloodfilter.

FIG. 4 is a cross-sectional view of a filter member of the blood filterin FIG. 3.

FIG. 5 is a schematic view of an artificial pump-oxygenator circuit.

FIG. 6 is a perspective view of the lower portion of the membraneoxygenator depicted in FIG. 2.

FIG. 7 is a right-side view of the lower portion of the membraneoxygenator depicted in FIG. 2.

BEST MODE FOR CARRYING OUT THE INVENTION

The medical instrument according to the present invention has a bloodcontact portion formed of a hydrophobic material, part or the entiretyof which has deposited thereto a surface-active agent safe to a humanbody.

The medical instruments include blood lines used in an extracorporealblood circuit, blood processing units attached thereto, etc.Specifically, the medical instruments include oxygenators, bloodfilters, heat exchangers, blood reservoirs, and blood lines as used inartificial pump-oxygenator circuits. Also included are dialyzers, bloodlines, and adsorption type blood cleaning units as used in artificialdialysis circuits.

Referring to FIG. 1, there is illustrated an embodiment of the medicalinstrument of the present invention which is applied to a membraneoxygenator.

The membrane oxygenator 1 includes a tubular housing 2, a bundle ofgas-exchange hollow fiber membranes 3 received in the tubular housing 2,and partitions 4 and 5 liquid-tightly securing the opposed ends of thehollow fiber membranes 3 against the housing 2. The interior of thetubular housing 2 is divided into a first fluid chamber, that is, bloodchamber 12 and a second fluid chamber, that is, gas chamber. The tubularhousing 2 is provided with a first fluid inlet, that is, blood inlet 6and a first fluid outlet, that is, blood outlet 7 in communication withthe blood chamber 12. A cap-like gas introducing port 10, which has asecond fluid inlet, that is, gas inlet 8 in communication with the gaschamber defined by the interior space of the hollow fiber membranes 3,is mounted above the partition 4 onto the end of the tubular housing 2.Thus a gas inlet chamber 13 is defined by the outside surface of thepartition 4 and the inside surface of the gas introducing port 10. Thegas inlet chamber 13 communicates with the gas chamber defined by theinterior space of the hollow fiber membranes 3. Similarly, a cap-likegas discharging port 11, which has a second fluid outlet, that is, gasoutlet 9 in communication with the interior space of the hollow fibermembranes 3, is mounted below the partition 5. Thus a gas dischargingchamber 14 is defined by the outside surface of the partition 5 and theinside surface of the gas discharging port 11. The oxygenator of thetype wherein blood is passed outside the hollow fiber membranes causesonly a small pressure loss. Then blood can be fed to the oxygenator bydrainage of blood assisted by only the head between the human body andthe oxygenator, without the need for a blood feed pump located upstreamof the oxygenator in the circuit.

The hollow fiber membranes 3 are porous membranes having an insidediameter of 100 to 1,000 μm, a wall thickness of 5 to 200 μm, preferably10 to 100 μm, and a porosity of 20 to 80%, preferably 30 to 60%, withpores having a diameter of 0.01 to 5 μm, preferably 0.01 to 1 μm. Theporous membranes are formed from hydrophobic polymeric materials such aspolypropylene, polyethylene, polysulfone, polyacrylonitrile,polytetrafluoroethylene, and cellulose acetate. More preferably they areformed from polyolefinic resins, most preferably polypropylene.Preferred membranes are those having fine pores formed in the wall by astretching or solid-liquid layer separation method.

Instead of porous membranes, the hollow fiber membranes 3 may bediffusion membranes formed of a material having a high permeability tooxygen and carbon dioxide such as silicone rubber.

The tubular housing 2 is formed of hydrophobic synthetic resins such aspolycarbonate, acryl-styrene copolymers, and acryl-butylene-styrenecopolymers. The housing 2 may be cylindrical, for example, and ispreferably transparent. The housing of transparent material permits easyvisual observation.

In this embodiment, a large number of, for example, about 5,000 to100,000 porous hollow fiber membranes 3 extend parallel in the housing 2in an axial direction thereof. The hollow fiber membranes 3 are securedto the opposite ends of the housing 2 by the partitions 4 and 5 in aliquid tight manner, with the opposite ends of the hollow fibermembranes 3 kept open. The partitions 4 and 5 are formed of a pottingcompound such as polyurethane or silicone rubber. The interior region ofthe housing 2 interposed between the partitions 4 and 5 is thus dividedinto the gas chamber defined inside the hollow fiber membranes 3 and theblood chamber 12 defined outside the hollow fiber membranes 3.

The gas introducing port 10 having the gas inlet 8 and the gasdischarging port 11 having the gas outlet 9 are mounted on the housing 2in a liquid tight manner. These ports are also formed of a hydrophobicsynthetic resin as used in the housing. Attachment of them to thehousing 2 may be carried out by fusing through ultrasonic, radiofrequency or induction heating, adhesive bonding, or mechanicalengagement. A fastening ring (not shown) may also be used for attachmentpurposes. With the above construction, all the portions (the insidesurface of the housing 2 and the outside surface of the hollow fibermembranes 3) of the membrane oxygenator 1 to be in contact with bloodare formed of hydrophobic material.

Although the foregoing description is made in connection with the hollowfiber oxygenator, the present invention is not limited thereto and isalso applicable to those oxygenators having gas-exchange membranes offlat shape.

A surface-active agent safe to a human body is deposited onto theentirety of the blood contact portions of the membrane oxygenator 1.

The surface-active agents used in the present invention are preferablynonionic surface-active agents, most preferably polyether type polymericsurface-active agents. The polyether type polymeric surface-activeagents are usually block copolymers of propylene oxide and ethyleneoxide having a molecular weight of about 1,000 to several 10,000. Theyare classified into pluronic and tetronic types and a number of variantsare available depending on the number of functional groups, the type ofalkylene oxide, and the order of blocks. Preferred surface-active agentsare of pluronic type. The polymeric surface-active agent of pluronictype has the following structure:

    HO(C.sub.2 H.sub.4 O).sub.a (C.sub.3 H.sub.6 O).sub.b (C.sub.2 H.sub.4 O).sub.c H

These surface-active agents are characterized in that they have a highmolecular weight ranging from 1,000 to several 10,000, that a widevariety of compounds having a varying molecular weight, HLB(hydrophilic-lipophilic balance) and other properties are formed byproperly controlling or combining the molecular weight of a hydrophobicgroup and the amount of ethylene oxide added, that they are generallyless foamable, that they are resistant to acids, alkalis, peroxides, andmetal ions, and that they are fully safe to a human body as seen fromtheir use as a medical agent which is an antihemolytic agent forextracorporeal circulation.

The deposition of the surface-active agent means that a dry deposit ofthe surface-active agent is present on the blood contact portion,particularly on the surface of the gas-exchange membrane to be incontact with blood. It is preferred that the surface-active agent bedeposited onto the entirety of the blood contact portion although thesurface-active agent may be deposited onto part of the blood contactportion. For example, the surface-active agent may be deposited ontoonly the outside surface of the hollow fiber membranes 3, only theinside surface of the housing 2, or only the inside surface of the bloodinlet or outlet of the housing 2. In this case, when a priming liquid ispassed from the blood inlet or outlet, the surface-active agent isdissolved in the priming liquid and then distributed over the entiretyof the blood contact portion of the oxygenator.

Since the surface-active agent is deposited onto the blood contactportion of the oxygenator 1, the blood contact portion has a reducedcontact angle with respect to liquid and thus exhibits improvedwettability. This ensures efficient priming because liquid can be passedover the blood contact portion for priming without leaving fine bubblesadhered on the surface thereof. Where the gas-exchange membranes arehollow fiber membranes, complete priming can be accomplished without theair-blocking phenomenon whereby air locally stagnates.

Next, an embodiment in which the medical instrument of the presentinvention is applied to a blood reservoir and a heat exchanger isdescribed with reference to FIG. 2 showing an artificial oxygenatorapparatus having a blood reservoir and a heat exchanger combinedtherewith.

The artificial oxygenator apparatus 30 includes a blood reservoir 31, anoxygenator 1, and a heat exchanger 50.

The blood reservoir 31 includes a housing 39 having a blood inlet 32, ablood reserving portion 39a and a blood outlet 33 (see FIG. 7), and alid 38 mounted on the housing 39 and having a medication infusing port35 thereon.

The blood reservoir 31 is constituted by a rigid member which is formedof a hydrophobic synthetic resin such as rigid vinyl chloride resgin,styrene resin, and carbonate resin. The housing 39 is preferablytransparent so that the blood reserved therein can be readily observedvisually. The blood reservoir may be a closed type flexible bloodreservoir which is prepared in a bag form from a flexible syntheticresin such as flexible vinyl chloride resin, flexible polyethyleneresin, and flexible polypropylene resin.

The blood inlet 32 of the blood reservoir 31 is in communication withthe blood outlet 7 of the oxygenator 1. Preferably the blood reservoir31 is further provided with a blood entry portion in communication withthe blood inlet 32. The blood entry portion forms a blood flowpaththrough which the blood entering the blood reservoir 31 from the bloodinlet 32 flows to the blood reserving portion 39a, and thus has a bottomwhich is located at a level higher than the blood reservoir tank, butsubstantially equal to the blood inlet 32. The bottom may be of eitherflat or semicylindrical shape, although the flat shape is preferredbecause it permits easy installation of a debubbling member 41 to bedescribed hereinafter.

The debubbling member 41 is preferably disposed in the blood entryportion so as to traverse the blood flowpath. Upon receipt ofbubble-containing blood, the debubbling member 41 functions to removebubbles from the incoming blood to deliver bubble-free blood to theblood reserving portion 39a. The debubbling member 41 is generally afoam which removes bubbles by allowing bubbles to grow by virture of itshydrophobic nature. The foam is a three-dimensional reticulated body.The debubbling member 41 is preferably placed in close contact with thebottom and side surfaces of the blood entry portion of the bloodreservoir 31 such that all the incoming blood may contact the debubblingmember (no blood flowpath out of contact with the debubbling member isformed). The upper end of the debubbling member 41 need not necessarilybe in close contact with the lid 38 of the blood reservoir 31 althoughthe upper end of the debubbling member 41 is preferably in close contactwith the lid 38 in order to prevent movement of the debubbling member 41and overflow of blood beyond the upper end of the debubbling member 41.Further, the housing is preferably provided on its inside surface with aretainer 43 in order to prevent movement of the debubbling member 41.The retainer 43 is a rib projecting from the inside surface of thehousing 39. Four retainers are formed in total to hold the debubblingmember 41 at its ends therebetween. The rib which forms the retainer 43may preferably be of a linear continuous shape.

The foam used for the debubbling member 41 may include urethane,cellulose and nylon foams. The surface-active agent previously mentionedis deposited on the inside surface of the housing 39 which is a bloodcontact portion of the blood reservoir 31, preventing bubbles fromadhering to the inside surface of the housing upon priming. Preferably,the surface-active agent is further deposited on the debubbling member41.

In the embodiment shown in FIG. 2, the oxygenator 1 is the same as thatshown in FIG. 1. The liquid-tight connection between the blood outlet 7of the oxygenator 1 and the blood inlet 32 of the blood reservoir 31 maybe accomplished, for example, by liquid-tight engagement includingthreaded engagement, tapered engagement, and engagement through anO-ring, ultrasonic or radio frequency welding, or adhesive bonding.

To the blood inlet of the oxygenator 1 is connected a heat exchanger 50.The heat exchanger 50 includes a plurality of spaced-apart heat exchangetubes 55 extending parallel in a casing 54 in a longitudinal directionthereof. The opposite ends of the heat exchange tubes 55 areliquid-tightly secured to the side wall of the casing 54 by partitions(not shown) with their open ends kept unblocked. The casing 54 isprovided on its side wall with a blood inlet port 57 in communicationwith a space 56 which is defined by the partitions, the inside wall ofthe casing 54, and the outside wall of the heat exchange tubes 55. Thespace 56 is in communciation with the blood inlet of the oxygenator 1.Further, the interior space of the heat exchange tubes 55 which isliquid-tightly separated from the space 56 is in communciation with aheat-exchange medium inlet port 63 (see FIG. 6) provided in the casing54 outside one partition, and a heat-exchange medium outlet port 64 (seeFIG. 6) provided in the casing 54 outside the other partition. In thisheat exchanger 50, blood enters the heat exchanger 50 through the bloodinlet port 57 and flows outside the heat exchange tubes 55 whileheat-exchange medium (for example, warm or cool water) passes throughthe heat exchange tubes 55 to warm or cool the blood. Alternatively, theheat exchanger may be of the type in which blood is passed through heatexchange tubes while heat-exchange medium is passed outside the heatexchange tubes.

The surface-active agent previously mentioned is deposited onto theinside surface of the casing 54 and the outside surface of the heatexchange tubes 55 which constitute blood contact portions of the heatexchanger 50. The surface-active agent need not be deposited onto theheat exchange tubes 55 if they are nearly hydrophilic.

In this artificial oxygenator apparatus, the heat exchanger 50 and theblood reservoir 30 are provided with ports 59 and 61, respectively,through which temperature sensing probes are inserted.

It is to be noted that in the present invention, the deposition of thesurface-active agent on the blood contact portion need not be uniformand the only requirement is that the surface-active agent be depositedon the blood contact portion. The present invention is not limited tothe deposition of the surface-active agent on the blood contact portionof the oxygenator, and the surface-active agent may be deposited ontoonly the heat exchanger of a heat exchanger built-in oxygenator or onlythe reservoir of a reservoir built-in oxygenator. Preferably, thesurface-active agent is deposited all over the instrument. Even when thesurface-active agent is deposited on part of the instrument, entry ofpriming liquid causes the agent to be dissolved and delivered downstreamand further circulation of the priming liquid eventually preventsadhesion of bubbles all over the blood contact portion.

Next, an embodiment in which the medical instrument of the presentinvention is applied to a blood filter is described by referring toFIGS. 3 and 4.

The blood filter 70 is to be incorporated in the artificialpump-oxygenator circuit shown in FIG. 5 and functions to remove bubblesand foreign particles from blood passing through the circuit.

As shown in FIGS. 3 and 4, the blood filter 70 includes a cylindricalhousing 72 formed of a hydrophobic resin such as polycarbonate,polypropylene, polyethylene, styrene-butadiene (SB) resin, andmethylene-butadiene-styrene (MBS) resin, and a filter member 79 receivedin the housing 72 and interposed between blood inlet and outlet 75 and78 connected to the housing 72. To the housing 72 is liquid-tightlysecured a cover 73 having at its top a communication port 83 to whichvalve means, for example, a three-way cock is connected. The blood inlet75 is tangentially connected to the cylindrical housing 72 such thatbubble-containing blood flow may not go straight to the filter member79. Then blood enters the housing 72 to form a swirl flow.

The filter member 79 is fabricated, as shown in FIG. 4, by preparing ascreen mesh 80 formed of a hydrophobic synthetic resin such aspolypropylene, polyethylene, and polyester and having a mesh size of 20to 50 μm, sandwiching the mesh between nets 81, 81 formed ofpolypropylene, polyethylene, polyester or the like, and tucking thesandwich to form pleats while rounding into a cylindrical shape. A seal79a is formed at the upper end of the filter member 79 of cylindricalshape by casting synthetic fibers, for example, polyolefines such aspolypropylene and polyethylene, and elastomers such as ethylene vinylacetate (EVA), polyurethane, styrene-butadiene-styrene (SBS) elastomerand silicone rubber. The filter member 79 is received in the housing 72with the seal 79a of the filter member 79 placed atop. Another seal 79bis formed at the lower end of the filter member 79 by casting a similarresin to those described above and is placed in close contact with thebottom of the housing 72. A tubular retainer 77 having a closed bottomis inserted into the bore of the filter member 79 to maintain the shapethereof. A conical sealing member 76 is disposed over the seal 79a ofthe filter member 79.

In the blood filter 70 of the above-mentioned structure, blood entersthe cylindrical housing 72 through the blood inlet 75 in a tangentialdirection to form a swirl flow within the housing 72. Bubbles areseparated by allowing bubbles of a small mass carried on the swirl flowof blood to collect toward the center of rotation by virture of acentrifugal force. The filter member 79 prevents passage of foreignparticles of a large mass.

The surface-active agent previously mentioned is deposited onto theblood contact portion of the blood filter 70 (the inside surface of thehousing 72 and the surface of the filter member 79). Then the bloodcontact portion has a reduced angle of contact with liquid and exhibitsimproved wettability. Priming liquid can be passed to carry outsatisfactory priming without leaving fine bubbles adhered to the surfaceof the blood contact portion. Particularly when the surface-active agentis deposited onto the surface (inside or outside surface or both) of thefilter member, no air is locally left on the surface of the filtermember, preventing any reduction of the effective surface area of thefilter member by residual air and hence any increase of pressure loss.Priming of the blood filter 70 is generally carried out by introducingliquid into the housing 72 through the blood outlet 78 at the lower endof the housing 72 with the communication port 83 kept open, and forcingair upward in the housing 72 to empty the housing of air. Thus thesurface-active agent is preferably deposited onto the inside surface ofthe filter member 79.

Next, the method for fabricating a medical instrument according to thepresent invention will be described.

The method for fabricating a medical instrument according to the presentinvention comprises steps of assembling a medical instrument having ablood contact portion formed of a hydrophobic material, and contacting aliquid containing a surface-active agent safe to a human body to theblood contact portion, followed by drying, leaving the surface-activeagent deposited onto the blood contact portion.

The medical instruments includes blood lines, oxygenators, etc. asdescribed above. The above mentioned surface-active agents mayadvantageously be used.

The liquid containing the surface-active agent may be contacted to theportion of the medical instrument to be in contact with blood, forexample, by charging the blood contact portion of the medical instrumentwith the surface-active agent containing liquid, introducing a mixtureof gas and mist of the surface-active agent containing liquid, or anyother method. Preferably, the blood contact portion of the medicalinstrument is filled with the surface-active agent containing liquidwhile each end of the medical instrument is sealed to prevent leakage ofthe liquid.

When a liquid (solution or dispersion) containing a polyether typepolymeric surface-active agent as previously mentioned is employed asthe surface-active agent, it is preferred to use a solution containing0.001 to 10%, more preferably 0.002 to 2.0% of the surface-active agent.The solvent may be aqueous solvents, especially water. Also employableis a mixture of water and ethyl alcohol.

The surface-active agent may be deposited onto the blood contact portionof an oxygenator, for example, by contacting a surface-active agentcontaining liquid to the blood contact portion followed by drying,blowing a surface-active agent powder or surface-active agent containingliquid along with air to deposit the agent onto the bloodcontact-portion, or any other method. In this way, according to thepresent invention, a medical instrument in which the surface-activeagent is deposited onto the blood contact portion is obtained afterdrying.

In case the medical instrument is an oxygenator as described above,after completion of assembly of the oxygenator and prior tosterilization, a leak test is generally carried out by filling the bloodchamber of the oxygenator with water and pressurizing the charged waterto detect the presence of pinholes in porous membranes or leakage ofliquid at the connection between gas-exchange membranes and the housing(and the partitions), or the like. When the medical instrumentfabricating method of the present invention employs liquid charging asthe step of contacting the surface-active agent containing liquid, theleak test may be carried out on the oxygenator at the same time. In thiscase, the oxygenator fabricating method involves the steps of assemblinga membrane oxygenator 1 comprising a housing 2 the interior of which isdivided into blood and gas chambers by hydrophobic porous membranes 3disposed in the housing 2, then charging the blood chamber with liquidcontaining the surface-active agent, keeping the blood chamber under apressure or the gas chamber under a negative pressure, and thereafterremoving the liquid, followed by drying.

If pinholes are present in the membranes, leakage of water becomes easythrough the pinholes in the leak test, increasing the sensitivity ofpinhole detection. This is particularly effective when the membraneshave a contact angle of up to 90°. Contact angles of up to 90° indicatethat the membrane surface is more stable in contact with water than withair. Then it is only the surface tension of liquid that prevents theprogress of wetting. Since the surface tension facilitates the progressof wetting along a convergent path, priming operation is done completelyupon use. Since the progress of wetting along a divergent path isinhibited, liquid does not leak through pores in porous hollow fibermembranes 3. Pinholes are considered intermediate. Even in the case ofporous membranes, the membranes are not wetted in principle if theircontact angle is more than 0°. The membranes desirably have a contactangle of at least 45° because the shape of pores is indefinite.

At the end of the leak test, the oxygenator is emptied of the liquid anddried. Drying may preferably be carried out by blowing warm air. Simpleair drying may also be employed.

Although the foregoing description is made in conjunction with amembrane oxygenator, the present invention may be similarly applied toheat exchangers, blood filters, blood lines, or the like.

Next, examples of the present invention will be described.

EXAMPLE 1

A hollow fiber bundle was prepared by randomly choosing porous hollowfibers of polypropylene (an inner diameter of 200 μm, a wall thicknessof 50 μm, an average pore diameter of 700 Å, and a porosity of 40%), andgathering about 35,000 fibers into a bundle. The hollow fiber bundle wasplaced in a housing of a shape as shown in FIG. 1. Polyurethane was castthrough the blood inlet and outlet of the housing to secure the oppositeends of the bundle to the opposite ends of the housing, obtaining ahollow fiber membrane oxygenator (an effective membrane area of 2.7 m²)as shown in FIG. 1.

A leak test was carried out by filling the blood contact portion (theblood side) with an aqueous solution containing 0.1% of a polyether typepolymeric surface-active agent (trade name: Pluronic F68, WyandotteCorp., U.S.A. having the structural formula: ##STR1## and pressurizingthe solution under an atmospheric pressure for 5 minutes. The oxygenatorwas emptied of the solution and then dried by feeding air at 45° C. at aflow rate of 50 l/min. for about 180 minutes. There is obtained anoxygenator having the surface-active agent deposited all over the bloodcontact portion thereof.

The weight of the oxygenator was measured both before and after thedeposition of the surface-active agent to find that about 50 mg of thesurface-active agent was deposited.

COMPARATIVE EXAMPLE 1

A hollow fiber oxygenator designated Comparative Example 1 wasfabricated by the same procedure as in Example 1 except that the step ofdepositing the surface-active agent was omitted.

EXPERIMENT 1

The following experiment was carried out on the oxygenators of Example 1and Comparative Example 1. An experimental circuit was constructed byplacing a reservoir tank containing blood at a high level, connectingthe tank to the blood inlet of the oxygenator, connecting a short tubeto the blood outlet of the oxygenator, and connecting the other end ofthe tube to a tank for collecting outgoing blood. The experimentalcircuit was designed such that it was only the oxygenator that caused apressure loss, and no other component inviting a pressure loss waspresent downstream of the oxygenator. The head between the bloodreservoir tank and the oxygenator was set so as to allow blood to flowat a flow rate of 4 l/min. The blood used was an ACD and heparin-addedbovine blood having a hemoglobin concentration of 12 g/dl and an oxygensaturation of 50%.

Under the above-mentioned conditions, blood was passed through theoxygenators of Example 1 and Comparative Example 1 to determine apressure loss and an oxygen saturation. While blood was being passedthrough the oxygenators of Example 1 and Comparative Example 1, impactwas applied to the housings (by striking several times with forceps).Then the pressure loss and oxygen saturation were measured. The resultsare shown in Table 1.

                  TABLE 1                                                         ______________________________________                                                    Pressure                                                                      loss (mmHg)                                                                            Oxygen saturation (%)                                    ______________________________________                                        Example 1     20         95                                                   Comparative Example 1                                                                       13         85                                                   After impact                                                                  Example 1     20         95                                                   Comparative Example 1                                                                       20         95                                                   ______________________________________                                    

EXAMPLE 2

A housing body and a cover as shown in FIG. 3 were prepared frompolycarbonate. The housing had a volume of about 200 ml. A filter memberwas prepared by sandwiching a polyester mesh having a mesh size of 40 μmbetween a pair of upper and lower polyester nets, and tucking pleats inthe sandwich as shown in FIG. 4. The filter member had a surface area ofabout 700 cm². The upper and lower ends of the filter member were sealedwith a polyurethane. A tubular member having a disk-like flange at thetop and tapered to the closed bottom was inserted into the filter memberfrom the top. A conical sealing member was secured to the flange fromabove. The lower end of the filter member was bonded to the inside lowerend of the housing with a polyurethane. Finally, the cover was bonded tothe housing body, completing a blood filter of the structure shown inFIG. 3.

The blood filter was entirely filled with an aqueous solution containing0.01% of a polyether type polymeric surface-active agent (trade name:Pluronic F68, Wyandotte Corp., U.S.A. having the structural formula:##STR2## by introducing the solution through the blood outlet at thelower end of the housing. Thereafter, the filter was emptied of thesolution and then dried by feeding air at 45° C. at a flow rate of 50l/min. for about 60 minutes. There is obtained a blood filter having thesurface-active agent deposited all over the blood contact portionthereof.

EXAMPLE 3

A blood filter was fabricated by the same procedure as in Example 2except that the aqueous solution of surface-active agent had aconcentration of 0.005%.

EXAMPLE 4

A blood filter was fabricated by the same procedure as in Example 2except that the aqueous solution of surface-active agent had aconcentration of 0.002%.

COMPARATIVE EXAMPLE 2

A blood filter designated Comparative Example 2 was fabricated by thesame procedure as in Example 2 except that the step of depositing thesurface-active agent was omitted.

EXPERIMENT 2

The blood filters of Examples 2, 3 and 4 and Comparative Example 2 weresubjected to the following experiment. With the blood inlet of the bloodfilter closed and the communication port open, water was introduced intothe blood filter through the blood outlet at a flow rate of 2,000ml/min. The time taken from the start of water introduction until watercame out of the filter member was measured. The result are shown inTable 2.

                  TABLE 2                                                         ______________________________________                                                        Time (sec.)                                                   ______________________________________                                        Example 2         3                                                           Example 3         4                                                           Example 4         5                                                           Comparative Example 2                                                                           26                                                          ______________________________________                                    

Industrial Applicability

Since the medical instrument according to the present invention has ablood contact portion formed of a hydrophobic material, wherein asurface-active agent safe to a human body is deposited onto part or theentirety of the blood contact portion, the blood contact portion has areduced angle of contact with liquid and exhibits improved wettability,ensuring that the medical instrument is fully primed by introducingliquid into the instrument without leaving fine bubbles adhered to thesurface of the blood contact portion.

Since the method for fabricating a medical instrument according to thepresent invention comprises steps of assembling a medical instrumenthaving a blood contact portion formed of a hydrophobic material, andcontacting a liquid containing a surface-active agent safe to a humanbody to the blood contact portion, followed by drying, leaving thesurface-active agent deposited onto the surface of the blood contactportion, this ensures that the surface-active agent is steadily andreadily deposited onto the blood contact portion of hydrophobicmaterial.

We claim:
 1. A medical instrument comprising a blood contact portionformed of a hydrophobic material and having a non-toxic, nonionicsurface-active agent deposited onto said blood contact portion, whereinsaid surface-active agent is a polyether consisting essentially of ablock copolymer of propylene oxide and ethylene oxide.
 2. The medicalinstrument according to claim 1, wherein said medical instrumentcomprises a membrane oxygenator having a hydrophobic gas-exchangemembrane and wherein said nonionic surface-active agent is depositedonto a blood contact portion within said membrane oxygenator.
 3. Themedical instrument according to claim 2, wherein said hydrophobicgas-exchange membrane comprises a porous membrane.
 4. The medicalinstrument according to claim 2, wherein said hydrophobic gas-exchangemembrane comprises a porous hollow fiber membrane.
 5. The medicalinstrument according to claim 2, wherein said membrane oxygenatorcomprises:a housing having a blood inlet and a blood outlet; a hollowfiber membrane bundle comprising a plurality of gas-exchange hollowfiber membranes provided in said housing; a pair of partitions, saidpartitions liquid-tightly securing opposite ends of said hollow fiberbundle to said housing; a blood chamber defined by said partitions, aninside surface of said housing, and an outside surface of said hollowfiber membranes; a gas chamber defined in the interior of said hollowfiber membranes; a gas flowpath-defining member disposed outside atleast one of the partitions and having a gas inlet in communication withsaid gas chamber; and a gas outlet means communicating with said gaschamber.
 6. The medical instrument according to claim 1, wherein saidmedical instrument comprises a blood filter having a hydrophobicmembrane and wherein said nonionic surface-active agent is depositedonto a blood contact portion within said blood filter.
 7. The medicalinstrument according to claim 1, wherein said surface-active agent isdissolved in a priming liquid.
 8. The medical instrument according toclaim 1, wherein said surface-active agent has a molecular weight fromabout 1,000 to several 10,000.
 9. The medical instrument as described inclaim 8, wherein said surface-active agent has the following structuralformula:

    HO(C.sub.2 H.sub.4 O).sub.a (C.sub.3 H.sub.6 O).sub.b (C.sub.2 H.sub.4 O).sub.c H.


10. The medical instrument according to claim 8, wherein saidsurface-active agent has the following formula: ##STR3##
 11. The medicalinstrument according to claim 8, wherein said surface-active agent is apolyether which consists of a block copolymer of propylene oxide andethylene oxide and having terminal hydroxyl groups.
 12. A method forfabricating a medical instrument comprising the steps of:assembling amedical instrument having a blood contact portion formed of ahydrophobic material; contacting a liquid containing a non-toxic,nonionic surface-active agent to said blood contact portion, saidsurface-active agent being a polyether consisting essentially of a blockcopolymer of propylene oxide and ethylene oxide; and drying saidsurface-active agent to deposit said surface-active agent onto a surfaceof said blood contact portion.
 13. The method for fabricating a medicalinstrument according to claim 12, wherein said medical instrumentcomprises a membrane oxygenator comprising a housing having an interiorwhich is divided into a blood chamber and a gas chamber by a hydrophobicgas-exchange membrane disposed in the housing,said method comprises thesteps of assembling said membrane oxygenator, charging said bloodchamber with a solution having a surface-active agent added thereto,maintaining a positive pressure differential between the blood chamberand the gas chamber, removing said solution, and drying said solution.14. The method for fabricating a medical instrument according to claim13, wherein said gas-exchange membrane comprises a porous membrane. 15.The method for fabricating a medical instrument according to claim 13,wherein said membrane oxygenator comprises:a housing; a hollow fibermembrane bundle comprising a plurality of gas-exchange hollow fibermembranes provided in said housing; a pair of partitions, saidpartitions liquid-tightly securing opposite ends of said hollow fiberbundle to said housing; a blood chamber defined by said partitions, aninside surface of said housing, and an outside surface of said hollowfiber membranes; a gas chamber defined in the interior of said hollowfiber membranes; a gas flowpath-defining member disposed outside atleast one of the partitions and having a gas inlet in communication withsaid gas chamber; and a gas outlet means communicating with said gaschamber.
 16. The method for fabricating a medical instrument accordingto claim 12, wherein said surface-active agent is dissolved in a primingliquid.
 17. The method for fabricating a medical instrument according toclaim 12, wherein said surface-active agent has a molecular weight fromabout 1,000 to several 10,000.
 18. The method for fabricating a medicalinstrument according to claim 17, wherein said surface-active agent hasthe following structural formula:

    HO(C.sub.2 H.sub.4 O).sub.a (C.sub.3 H.sub.6 O).sub.b (C.sub.2 H.sub.4 O).sub.c H.


19. The method for fabricating a medical instrument according to claim17, wherein said surface-active agent has the following formula:##STR4##
 20. The method for fabricating a medical instrument accordingto claim 17, wherein said surface-active agent is a polyether whichconsists of a block copolymer of propylene oxide and ethylene oxide andhaving terminal hydroxyl groups.